Fraunhofer Gesundheit’s Post

While RNA molecules' effects on hematopoietic tumor cells remained elusive due to delivery challenges, a recent study has made significant headway. Here's what you need to know: 1️⃣ The study explored a novel glucose-attached reversibly ionic oligonucleotide-based nanoparticle (RION) designed to carry a chemically modified miR143-3p, aptly named miR143#12 (named Glu-RION-miR143#12). The nanoparticles are created by self-assembly involving base hybridization and electrostatic interaction via a functionalized chemically modified passenger strand. 2️⃣ Targeted Silencing: This delivery mechanism effectively introduced miR143#12 into hematopoietic tumor cells, silencing not just RAS but a broader network including Sos-1, Akt, ERK1/2, and ERK5. The result? Induced cell cycle arrest and promotion of apoptotic cell death. 3️⃣ Antiproliferative Action: The manner in which miR143#12 hindered the proliferation of hematopoietic tumor cells mirrored its effect on colon cancer KRAS-mutant DLD-1 cells. Most importantly, this action was exclusive to malignant cells, sparing non-malignant cells like human peripheral lymphocytes. The study shows that Glu-RION-miR143#12 holds remarkable promise as a nucleic acid medication, not just for primary hematologic malignancies but also for recurrent malignant hematopoietic cells with RAS mutations. 🔗 https://lnkd.in/edFsfczT #HematopoieticTumor #RNATherapy #CancerResearch #InnovationInMedicine #nanotechnology #nanoparticles #nanomaterials #nano

SNEAK PEEK: Researchers at the Indiana University School of Medicine relay the importance of oxygen conditions in preclinical cancer research. Using our Xvivo System® Model X3 hypoxia incubator, they found that cells cultured in ambient air display differential EGFR activation and were more sensitive to targeted therapies than those in physioxia. Their data emphasizes how physiologically relevant oxygen levels are imperative in cell culture in order to effectively develop therapies and identify drug targets. #cellculture #physioxia #xvivo #biospherix

Check out the recent talk below by Prof. Dmitry Gabrilovich, expert in myeloid cell biology, as he discusses MDSCs and the role they play in promoting tumour progression. Just drop me a message with any questions about the talk or wider resource!

Here are some thoughts about biological role of MDSC in cancer. I believe, the link provided, will get free access to this lecture.

🌟Myeloid cells, such as tumour associated macrophages and myeloid-derived suppressor cells (MDSC) are prevalent in the tumour microenvironment, and promote tumour progression by suppressing the immune response. ▶In his talk, Prof. Dmitry Gabrilovich, Executive Director and Chief Scientist at AstraZeneca, and expert in myeloid cell biology, discusses the complexity of targeting myeloid cells due to their functional redundancy while emphasizing the importance of understanding myeloid cell biology for effective therapies. He highlights the role of S100A9 as well as the downregulation of IFNAR1 in MDSCs on suppressive activity and discusses the possibility of targeting the ferroptosis pathway to improve tumour outcomes. Overall, his research reinforces the critical role of pathological myeloid cells in cancer progression and therapy. 👇Click below to access Prof. Gabrilovich’s talk in full as well as a host of others on related topics within The Biomedical & Life Sciences Collection. https://lnkd.in/ggRTnHbJ

Traditional methods of drug discovery, reliant on 2D cell cultures and animal models, struggle to accurately replicate human physiology and tumor microenvironments, leading to high failure rates in clinical trials and limited treatment efficacy. A recent study leveraged the BIO X bioprinter and a combination of CELLINK SKIN and CELLINK Bioink, to create sophisticated in vitro models of human skin cancer. These 3D models accurately mirrored the complexity of cutaneous squamous cell carcinoma (cSCC) and the human skin microenvironment, offering a more representative platform for drug testing. By demonstrating reduced drug sensitivity compared to traditional methods (spheroids and 2D models), this research highlights the potential of 3D bioprinting in opening new frontiers for preclinical cancer research and leading to more effective treatments and improved patient outcomes. Read the full publication: https://lnkd.in/dEz-medm #skin #cancerresearch #3dbioprinting #3Dmodels #spheroids #2Dmodels Maria Sklodowska-Curie National Research Institute of Oncology, Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

We are happy to share our new research highlight published in Cell Research about how tumor microenvironment pushes CD8 T cell towards exhaustion. https://lnkd.in/eNjm4rxT

Source: Discovery medicine The study explores the therapeutic potential of a long non-coding RNA called BLACAT1 in hypopharynx squamous cell carcinoma (HSCC). The researchers found that BLACAT1 is highly expressed in HSCC tumor tissues and is associated with advanced clinical stages, lymphatic invasion, and poor prognosis. In both in vitro and in vivo experiments, inhibiting BLACAT1 suppressed tumor growth and inhibited the proliferation, migration, and invasion of HSCC cells. The study also identified two proteins, STAT3 and PHB2, that bind to BLACAT1 and are involved in the development of HSCC. The findings suggest that BLACAT1 may serve as a potential therapeutic target for HSCC.

Dr. Neekkan Dey, a postdoc from J. Alan Diehl's group at the Department of Biochemistry, Case Comprehensive Cancer Center at Case Western Reserve University, has just had their research work accepted for publication in the Molecular Cancer Research Journal by AACR. The study, "miR-217 regulates normal and tumor cell fate following induction of Endoplasmic Reticulum Stress," unveils the intricate interplay of PERK-responsive microRNAs (miRNAs), miR-211 and miR-217, in deciding cell fate during acute ER stress. Check out the article here:

📃Scientific paper: Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy Abstract: Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, and acquire mesenchymal properties that mediate invasion and metastasis. Stromal cells and soluble mediators in the tumor microenvironment (TME) exhibit characteristic anti-inflammatory and protumorigenic activities. Ubiquitination, which is an essential and reversible posttranscriptional modification, plays a vital role in modulating the stability, activity and localization of modified proteins through an enzymatic cascade. This review was motivated by accumulating evidence that a series of E3 ligases and deubiquitinases (DUBs) finely target multiple signaling pathways, transcription factors and key enzymes to govern the functions of almost all components of the TME. In this review, we systematically summarize the key substrate proteins involved in the formation of the TME and the E3 ligases and DUBs that recognize these proteins. In addition, several promising techniques for targeted protein degradation by hijacking the intracellular E3 ubiquitin-ligase machinery are introduced. Discover the rest of the scientific article on es/iode ➡️https://etcse.fr/MUHn